|Publication number||US5242706 A|
|Application number||US 07/738,362|
|Publication date||Sep 7, 1993|
|Filing date||Jul 31, 1991|
|Priority date||Jul 31, 1991|
|Publication number||07738362, 738362, US 5242706 A, US 5242706A, US-A-5242706, US5242706 A, US5242706A|
|Inventors||Catherine M. Cotell, Douglas B. Chrisey, Kenneth S. Grabowski, James A. Sprague|
|Original Assignee||The United States Of America As Represented By The Secretary Of The Navy|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (15), Non-Patent Citations (8), Referenced by (108), Classifications (22), Legal Events (5)|
|External Links: USPTO, USPTO Assignment, Espacenet|
1. Field of the Invention
The present invention relates to a method and an apparatus for depositing biocompatible material onto a substrate, and to articles formed thereby. More particularly, the present invention provides a method and an apparatus for using a laser to deposit thin films of biocompatible material of controlled chemical composition and crystalline structure onto a substrate to provide articles which may be used as medical, dental or orthopedic implants, other medical devices designed for short- or long-term contact with human or animal tissue, or for other applications in which a biocompatible material is required in thin film form.
2. Description of the Prior Art
Medical implant devices are being increasingly used for a variety of purposes. Because living organisms generally reject any foreign matter, such devices should appear to be of natural or nonforeign material.
The design of prosthetics or other devices to be implanted in the human body must take into consideration mechanical integrity as well as biocompatibility. A number of biocompatible ceramic compositions exist, but all lack sufficient mechanical strength for use in load-bearing applications.
It has been proposed to solve this materials problem by coating a bulk material, chosen for its mechanical strength and corrosion resistance, with a thin film of biocompatible material. Such a biocompatible coating may be inert, in which case a fibrous capsule of tissue will surround the implant over time, or it may be porous, so as to encourage the ingrowth of tissue into the pores. Alternatively, such a biocompatible coating may be resorbable, i.e., it may be designed to dissolve over time and be replaced by the natural host tissue. A fourth category of biocompatible coatings includes bioactive materials that elicit a specific biological response at the interface of the material which results in the formation of a bond between the tissues and the material.
An example of a biocompatible material is hydroxylapatite, i.e., Ca10 (PO4)6 (OH)2, which is the primary chemical constituent of bone. Various attempts have been made to deposit hydroxylapatite films onto metal substrates, the hydroxylapatite acting as a resorbable biocompatible coating. Amorphous hydroxylapatite and calcium phosphate materials, e.g., α-tricalcium phosphate, β-tricalcium phosphate and tetracalcium phosphate are more resorbable than crystalline hydroxylapatite (HA).
Since the resorbability of a deposited film is a function of its local chemistry, as well as its crystal structure, a useful deposition technique for coating substrates with hydroxylapatite must allow for control of chemistry, crystallinity and morphology. Prior attempts to deposit hydroxylapatite films onto substrates have suffered from various drawbacks and limitations, as discussed below.
Plasma spraying has been used to coat both metal and ceramic substrates with hydroxylapatite films. (See Cook et al., J. Dental Research, vol. 65 (1986) p. 222.) A number of problems have been reported to result from the plasma-spraying process, however. Adhesion of the film to the substrates is poor, giving rise to failure of finished devices. Furthermore, plasma-spraying is a high temperature technique which is unsuitable for depositing films on substrates which may degrade at elevated temperatures. In addition, the high temperature nature of the plasma-spraying technique also tends to drive structural water from hydroxylapatite, leaving films comprising a small fraction of hydroxylapatite in a matrix of dehydrated hydroxylapatite, i.e., tricalcium phosphate (TCP).
Electrophoretic deposition has been used to deposit hydroxylapatite onto Ti-6Al-4V substrates. (See Ducheyne et al., Biomaterials, vol. 7 (1986) p. 97.) Adhesion of the film to the substrate is poor, and sintering at high temperatures is usually needed to provide satisfactory interfacial bonding. The high-temperature sintering tends to deplete the film of phosphorus due to the formation of Ti-P compound(s) at the substrate interface, and it tends to drive water from the hydroxylapatite.
Radio frequency magnetron sputtering deposition has been employed to deposit hydroxylapatite onto substrates. (See Ruckenstein et al., J. Colloid and Interface Science, vol. 96 (1983) p. 245.) However, sputtering deposition tends to drive water from the hydroxylapatite and sacrifices the crystallographic structure.
Ion Beam Sputtering has been employed to deposit hydroxylapatite on substrates, however, it generally yields films that are phosphorus-deficient and amorphous. (See Barthell et al., Materials Research Society Symposium Proceedings. vol. 110, (1989), p. 709 and Stevenson et al., ibid., p. 715.)
An object of the present invention is to provide techniques for depositing one or more films of one or more biocompatible materials onto a substrate, more particularly, techniques which make it possible to (1) control whether each deposited film is amorphous or crystalline (or a mixture of amorphous and crystalline), (2) control the morphology (porosity and substrate/film interface structure) of each deposited film, (3) (in the case of crystalline phases) control the ratio of phases in multicomponent systems, e.g., the ratio of HA to phosphate compounds (i.e., α- tricalcium phosphate, β-tricalcium phosphate and tetracalcium phosphate), (4) control the stoichiometry of each film, e.g., the Ca/P ratio of each deposited HA film (the theoretical Ca/P ratio for hydroxylapatite is 1.67), (5) control the resorbability of each deposited film, and (6) control the composition, crystal structure and morphology of multilayer films comprising biocompatible materials. Another object of the present invention is to provide such a technique which provides greater flexibility in the selection of process parameters, e.g., substrate temperature at deposition. A further object of the present invention is to provide such a technique in which good adhesion between the substrate and the deposited film is achieved. A further object of the present invention is to provide such a technique which provides the capability to deposit films in a variety of gaseous environments.
The present invention is also directed to coated articles formed according to such techniques and to an apparatus for carrying out such techniques.
In accordance with the present invention, there is provided a method for depositing bioceramic material onto a substrate, the method comprising exposing biocompatible material to a laser beam at a position adjacent to a substrate such that the bioceramic material is deposited onto the substrate.
The invention may be more fully understood with reference to the accompanying drawings and the following description. The invention is not limited to the exemplary embodiments and should be recognized as contemplating all modifications within the skill of an ordinary artisan.
FIG. 1 is a schematic drawing depicting one embodiment in accordance with the present invention.
FIG. 2 is a schematic drawing depicting a second embodiment in accordance with the present invention.
FIGS. 3, 4 and 5 are graphs of Ca/P ratios of films deposited in Examples 2, 3 and 4 (below), respectively.
In accordance with the present invention, there is provided a method and an apparatus for depositing biocompatible material onto a substrate by exposing the biocompatible material (target) to a laser beam at a position adjacent to the substrate. Henceforth, the phrase "laser-deposited" is used to mean striking a target with a laser beam so that material is ablated off of the target and onto the substrate.
The biocompatible material may generally comprise any suitable biocompatible material. A preferred biocompatible material is hydroxylapatite, the chemical formula of which is Ca10 (PO4)6 (OH)2. Other biocompatible materials which may be used include HA-like phases (i.e., calcium- and phosphorus-containing phases such as α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate), natural bone, other bioceramics, for example biologically active glasses, typically referred to as bioglasses, e.g., the compositions disclosed in U.S. Pat. Nos. 4,103,002, 4,159,358, 4,234,972, 4,478,904 and 4,775,646, the entire disclosures of which are incorporated herein by reference, fluorapatite and other biocompatible materials, e.g., polymethyl methacrylate, tetraethylene glycol dimethyl ether, and fluorocarbons. The biocompatible material may comprise a single biocompatible material or a mixture of biocompatible materials.
The biocompatible material (target) may generally be in any shape suitable for being exposed to a laser beam (for example, a pellet, disc, cylinder or sphere). The preferred condition of the biocompatible material (target) is a dense pellet. A particularly preferred pellet diameter is about 0.75 inch. In the case of biocompatible ceramics such as hydroxylapatite that are typically delivered in the form of powders suspended in buffer solutions, the powders may be dried in a vacuum oven and subsequently pressed into dense pellets. The preferred temperature range for the vacuum drying is <120° C. and the preferred range of pressures for the pressing procedure is 40,000-100,000 psi. The pellets may then be sintered preferably in O2 at a temperature preferably within the range of from 450° C. to 650° C. and cooled, preferably slowly, to room temperature.
The substrate is preferably corrosion-resistant, and it may generally comprise any suitable material, e.g., metal, alloy, ceramic and/or polymer material in any suitable shape. Preferred substrates include Ti-6Al-4V, other Ti alloys, essentially pure Ti, Si, GaAs, InP, GeSi, SiC, silastic, PVC, MgO, Al2 O3, stainless steels, Co-Cr alloys and synthetic rubbers such as latexes and silicone rubbers. Ti-6Al-4V is particularly preferred. The substrate is preferably mounted on a substrate holder. For depositing HA, the substrate holder is preferably electrically isolated, although for some applications, the substrate holder may be biased. The substrate can generally be of any desired shape and orientation. For instance, the shape can be regular (e.g., flat and planar, tubular) or irregular. For many applications of the present invention, the substrate is of irregular shape. The orientation can be crystallographically oriented, polycrystalline, or amorphous.
Any suitable laser source can be employed. In general, as discussed below, a short pulsed laser is particularly preferred in accordance with the present invention. For example, an excimer laser (e.g., ArF, KrF, XeF or XeCl) can be used, a KrF excimer laser being especially preferred. Other short pulsed lasers, e.g., Nd-YAG or CO2, could be used.
The biocompatible material (target) being exposed to the laser beam and the substrate are preferably positioned within a chamber having an environment whose temperature, pressure and chemical composition are controlled. Suitable environments according to the present invention include argon/water, oxygen, and other reactive gas mixtures (for example, those having a partial pressure of oxygen such as carbon monoxide/carbon dioxide, hydrogen, water) as well as inert gases, such as argon. Two particularly preferred environments in accordance with the present invention are argon/water and oxygen. For creating an argon/water environment, there may be provided a gas inlet port which passes through a bubbler before passing into a vacuum chamber--for creating an oxygen environment, there may be provided a gas inlet port which passes directly into a vacuum chamber. The background pressure within the chamber during a deposition may be within the range of from about 0-760 Torr; 0.3 Torr is a particularly preferred total pressure.
The distance between the target and the substrate is preferably within the range of from about 3 cm to about 10 cm. A particularly preferred distance is about 4 cm. In general, larger distances are more suitable for depositing on larger substrate areas. Distances of greater than 10 cm may be used if desired, for example, for depositing on larger surface areas.
The thickness of the deposited film is proportional to the number of laser pulses to which the target is exposed, and may be selected depending on the purpose for which the finished article is to be used.
The biocompatible material (target) may be mounted on any support means suitable for supporting the biocompatible material. In accordance with a preferred aspect of the present invention, the biocompatible material (target) is mounted on a moving support means, such as a rotating and/or translating shaft, such that different portions of the target are in the center of the laser beam at different times, thereby extending the useful lifetime of the target and providing enhanced film uniformity. A preferred rate of rotation (and the rate employed in the Examples which follow herein) is about 0.5 revolution per second. Such an arrangement allows for greater uniformity of deposition on the substrate. Instead of (or in addition to) moving the biocompatible material (target), the center of the laser beam could be moved to achieve similar effects. In general, larger areas may be coated by rastering the center of the laser beam across the target surface. In these cases, larger targets (diameters >0.75 inch) would be preferred. In accordance with one modification according to the present invention, the substrate may be manipulated (e.g., rotated and/or translated) during deposition to allow deposition on nonplanar or irregularly-shaped substrates.
In accordance with another preferred aspect of the present invention, the laser may be a pulsating laser (as mentioned above, short pulsed lasers are preferred according to the present invention). Lasers for use in accordance with the present invention generally emit light having a wavelength in the range of from about 193 nm to about 1100 nm, an energy in the range of from about 0.1 to about 10 J/cm2, a pulsewidth of from about 10-12 to about 10-6 second and a pulse repetition frequency of from about 0 to about 1000 Hz. In general, energy density (fluence) affects morphology--higher energies tend to produce deposited films which have larger particles and which are less dense. In the Examples which follow herein, there was employed a laser that emitted light having a wavelength of about 248 nm, an energy of about 250 mJ/pulse, a pulsewidth of about 30 ns and a pulse repetition frequency of about 20 Hz.
As the biocompatible material is being deposited, the substrate may be maintained at ambient temperature or may be heated to any temperature up to about 800° C. or higher. Any suitable heating means may be used for this purpose. For example, one or more radiant heaters may be positioned so as to heat the surface of the biocompatible film continuously as it is deposited on the substrate. Alternatively, the substrate holder may be heated, e.g., by a quartz lamp. As discussed below, for many applications, precise temperature control at the surface of deposition is required.
In accordance with one modification according to the present invention, the substrate may first be deposited by laser deposition (preferably pulsed) and then the biocompatible film may be deposited on the thus-formed substrate.
Referring to FIG. 1, which depicts a first system in accordance with the present invention, a pellet 10 of biocompatible material is affixed to a rotating shaft 11 positioned within a vacuum chamber 12. A laser from a laser source 13 is focused through a lens 14 onto the pellet 10. A substrate 15 is mounted on a substrate holder 16 which is heated by a quartz lamp 17. The temperature of the substrate holder is monitored by a thermocouple 18. A gas inlet port 19 allows introduction of the desired gas or gas mixture into the vacuum chamber 12. A bubbler 20 is provided in the gas line leading to the gas inlet port 19.
A laser deposition system according to the present invention may optionally further comprise an ion source. FIG. 2 depicts a laser deposition system like the one shown in FIG. 1, which further includes a Kaufman ion source 21. A suitable ion source is a Kaufman ion source employing inert gases such as Ar+ and/or reactive gases such as O2 + or CO+ operating at about 50-1500 eV. Such an ion source can be used to pre-clean substrates in situ, to improve the adhesion between the deposited film of biocompatible material and the substrate, and/or to densify the biocompatible material as it is being deposited. When employing an ion source in accordance with the present invention, the pressure in the deposition chamber must be adjusted according to the ion gun specifications. This may involve reducing the pressure below the preferred pressures for deposition in the absence of an ion source.
The laser deposition method and system according to the present invention has numerous advantages over prior methods and systems, and the articles formed by the method according to the present invention have numerous advantages over the prior articles. For example, the method according to the present invention can be conducted at room temperature, if desired, thereby avoiding problems associated with oxidation of the substrate, degradation of the substrate or the film due to annealing and elimination of structural water, e.g., from hydroxylapatite. Also, the method according to the present invention can be conducted in a wide variety of gaseous environments, including water vapor environments. This feature lends a degree of control over the stoichiometry of the films. Operational parameters can be selected so as to (1) control whether a deposited film of biocompatible material is amorphous, crystalline, or a mixture of amorphous and crystalline phases, (2) control the crystal structure of the deposited film, (3) control the morphology of the deposited film, (4) achieve desired stoichiometry, e.g., the ratios of calcium to phosphorus in a deposited HA film and/or (5) provide better adhesion between the deposited film and the substrate. Moreover, for deposition of HA, operational parameters can be selected so as to control how much calcium phosphate (tricalcium phosphate or tetracalcium phosphate) is in a crystalline phase. Those operational parameters include the chemical makeup of the environment within the chamber, the pressure within the chamber and the temperature at the surface of the substrate. In addition, by selecting laser conditions (e.g., energy density, wavelength, pulse rate), target fabrication procedures (e.g., composition, density, sintering temperature) and/or by using ion beam assisted pulsed laser deposition, one can control the porosity of the deposited film and enhance the adhesion of the film to the substrate.
The following Examples demonstrate applications of the present invention. The Examples also show how operational parameters can be controlled, and how those parameters can be selected so as to achieve specific desired characteristics in the finished products.
Using a system as shown in FIG. 1, films of hydroxylapatite were deposited by pulsed laser deposition on flat, planar, polycrystalline Ti-6Al-4V substrates heated to various temperatures (as set forth in Table 1) in a chamber environment of argon/water at a total pressure of 300 mTorr. The phases (determined in Example 1, as in Examples 2 and 5, by X-ray diffraction) of the resulting deposited films are set forth in Table 1, in which "ph" designates tetracalcium phosphate.
TABLE 1______________________________________Experi- Chamber Temperaturement Environment (°C.) Phase(s)______________________________________ 1 argon/water, 30 amorphous 300 mTorr 2 argon/water, 30 amorphous 300 mTorr 3 argon/water, 200 amorphous 300 mTorr 4 argon/water, 200 amorphous 300 mTorr 5 argon/water, 400 amorphous 300 mTorr 6 argon/water, 400 amorphous + HA 300 mTorr 7 argon/water, 400 amorphous + HA 300 mTorr 8 argon/water, 400 amorphous + HA 300 mTorr 9 argon/water, 400 amorphous + HA 300 mTorr10 argon/water, 400 HA 300 mTorr11 argon/water, 400 HA 300 mTorr12 argon/water, 400 HA 300 mTorr13 argon/water, 400 HA 300 mTorr14 argon/water, 400 HA 300 mTorr15 argon/water, 500 amorphous + HA 300 mTorr16 argon/water, 500 amorphous + HA 300 mTorr17 argon/water, 500 amorphous + HA 300 mTorr18 argon/water, 500 amorphous + HA 300 mTorr19 argon/water, 500 amorphous + HA 300 mTorr20 argon/water, 500 HA 300 mTorr21 argon/water, 500 HA + ph 300 mTorr22 argon/water, 500 amorphous + HA + ph 300 mTorr23 argon/water, 500 amorphous + HA + ph 300 mTorr24 argon/water, 600 HA 300 mTorr25 argon/water, 700 HA + ph 300 mTorr26 argon/water, 800 HA 300 mTorr27 argon/water, 800 HA + ph 300 mTorr______________________________________
Again using a system as shown in FIG. 1, films of hydroxylapatite were deposited by pulsed laser deposition on Ti-6Al-4V substrates heated to various temperatures (as shown in FIG. 3) in a chamber environment of argon/water at a total pressure of 300 mTorr. The Ca/P ratios (determined in this Example, as in Examples 3-5, by Rutherford Backscattering Spectrometry) for the deposited films and the phase(s) in those films are depicted in FIG. 3 (in which "am" designates amorphous and "ph" designates crystalline tetracalcium phosphate).
Again using a system as shown in FIG. 1, films of hydroxylapatite were deposited by pulsed laser deposition on Ti-6Al-4V substrates heated to various temperatures (indicated in FIG. 4) in chamber environments of oxygen (not using a bubbler 20 as shown in FIG. 1) or oxygen/water (indicated in FIG. 4) at a pressure of 300 mTorr. The Ca/P ratios for the deposited films are depicted in FIG. 4.
Using a system as shown in FIG. 1 (except that it did not include the bubbler 20), films of hydroxylapatite were deposited by 21 pulsed laser deposition on Ti-6Al-4V substrates heated to 500° C. or 600° C. (as shown in FIG. 5) in a chamber environment of oxygen at various total pressures (as shown in FIG. 5). The Ca/P ratios for the deposited films are depicted in FIG. 5.
Again using a system as shown in FIG. 1 (except that it did not include the bubbler 20), films of hydroxylapatite were deposited on Ti-6Al-4V substrates by pulsed laser deposition under temperature and pressure conditions as set forth in Table 2. the Ca/P ratios and the crystal structure and phases of the resulting articles are also shown in Table 2.
TABLE 2______________________________________Temperature, Oxygen Pressure, Ca/P°C. mTorr ratio Phase(s)*______________________________________ 50 300 1.38 --400 300 1.5 amorphous600 300 1.75 HA, (α-TCP)800 300 1.6 α-TCP, (HA)600 100 2.05 --600 10 2.85 --600 0 2.52 amorphous______________________________________ *The phase in smaller concentration is denoted by parenthesis. TCP designates tricalcium phosphate.
Using a system as shown in FIG. 1 (which had a bubbler in those experiments in which the environment included water), films of hydroxylapatite were deposited by pulsed laser deposition on MgO<100>, silastic, and Si<111> substrates (as identified in Table 3 below at temperatures and in environments as identified in Table 3. The Ca/P ratios for the deposited films are listed in Table 3, in which "ph" designates crystalline tetracalcium phosphate.
TABLE 3__________________________________________________________________________ Temperature Ca/PSubstrate °C. Environment Phase Ratio__________________________________________________________________________MgO<100> 30 300 mTorr O2 amorphousMgO<100> 600 300 mTorr O2 α-tricalcium phosphate + HAMgO<100> 800 300 mTorr O2 HA + phSilastic 30 300 mTorr Ar/H2 O amorphous 1.23Silastic 30 300 mTorr Ar/H2 O amorphous 0.95Silastic 250 300 mTorr Ar/H2 O amorphous 1.08Si<111> 400 300 mTorr Ar/H2 O HA 2.66Si<111> 400 300 mTorr Ar/H2 O HA 1.08__________________________________________________________________________
From the above and other Examples, the present inventors drew a number of conclusions as to general effects of various operational parameters on the resulting deposited film, as follow:
(1) to obtain pure crystalline HA films (i.e., with no amorphous hydroxylapatite and no tricalcium phosphate or tetracalcium phosphate) on Ti-6Al-4V or Si substrates, an argon/water chamber environment at a pressure of 300 mTorr and a temperature in the range of from about 400° C. to about 600° C. is preferred;
(2) in an argon/water chamber environment or an oxygen chamber environment at a total pressure of 300 mTorr, at temperatures below 400° C., the deposited films are generally amorphous, regardless of substrate;
(3) in an argon/water chamber environment, at temperatures greater than 600° C., at a total pressure of 300 mTorr, the deposited films on Ti-6Al-4V or Si frequently include tetracalcium phosphate and crystalline HA;
(4) in an oxygen chamber environment at a pressure of 300 mTorr, at temperatures between 400° C. and 700° C., the deposited films generally include crystalline HA and α-tricalcium phosphate, whereas at temperatures greater than 700° C., the deposited films generally include crystalline HA and β-tricalcium phosphate;
(5) in an oxygen chamber environment at a pressure of 300 mTorr, at temperatures below about 400° C., the deposited films are generally amorphous;
(6) in an oxygen chamber environment, at a pressure less than or equal to 100 mTorr and a temperature of 600° C., the deposited films are generally amorphous;
(7) in an oxygen chamber environment, the Ca/P ratio in deposited films tends to be higher at lower pressures;
(8) in an oxygen chamber environment at 300 mTorr, the Ca/P ratio in deposited films tends to be lower at lower temperatures;
(9) in an argon/water chamber environment, the Ca/P ratio in films deposited on Ti-6Al-4V or Si tends to be greater than the theoretical Ca/P ratio of HA;
(10) Ca/P ratios of films deposited at temperatures ≦250° C. in Ar/water at 300 mTorr on silastic substrates tend to be less than the theoretical Ca/P ratio of HA;
(11) presence of water vapor in the chamber environment generally enhances the likelihood of obtaining HA or the amount of HA;
(12) adhesion of deposited films to Ti-6Al-4V substrates tends to be better when deposited in an argon/water chamber environment than when deposited in an oxygen chamber environment; and
(13) adhesion of deposited films to Ti-6Al-4V substrates tends to be better when deposited at a temperature below 600° C. than when deposited at a temperature above 600° C.
Although the methods, apparatuses and articles in accordance with the present invention have been described in connection with preferred embodiments, it will be appreciated by those skilled in the art that additions, modifications, substitutions and deletions not specifically described herein may be made without departing from the spirit and scope of the invention as defined in the appended claims.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US3557795 *||Jun 19, 1968||Jan 26, 1971||Weck & Co Inc Edward||Suture provided with wound healing coating|
|US4702930 *||Nov 4, 1985||Oct 27, 1987||Battelle-Institute E.V.||Method of producing implantable bone replacement materials|
|US4790851 *||Mar 14, 1986||Dec 13, 1988||France Implant||Method for manufacturing surgical implants at least partially coated with a layer of a metal compound, and implants manufactured according to said method|
|US4794023 *||Jul 17, 1987||Dec 27, 1988||Permelec Electrode Ltd.||Process for producing a calcium phosphate compound coated composite material|
|US4871578 *||Apr 4, 1988||Oct 3, 1989||Mtu Motoren- Und Turbinen-Union Muenchen Gmbh||Hydroxylapatite coating on metal or ceramic|
|US4882196 *||Mar 24, 1987||Nov 21, 1989||Permelec Electrode Ltd.||Process for the production of a titanium composite materials coated with calcium phosphate compound|
|US4908030 *||Apr 29, 1987||Mar 13, 1990||Vent-Plant Corporation, Inc.||Method of manufacturing synthetic bone coated surgical implants|
|US4911953 *||Sep 29, 1988||Mar 27, 1990||Permelec Electrode Ltd.||Process for producing composite materials having a coating of calcium phosphate compound|
|US4944754 *||Apr 26, 1988||Jul 31, 1990||Vent-Plant Corporation||Method of manufacturing synthetic bone coated surgical implants|
|US4950294 *||May 2, 1988||Aug 21, 1990||Olympus Optical Co., Ltd.||Composite structure useful as artificial bones|
|US4970196 *||Aug 19, 1988||Nov 13, 1990||The Johns Hopkins University||Method and apparatus for the thin film deposition of materials with a high power pulsed laser|
|US4990163 *||Feb 6, 1989||Feb 5, 1991||Trustees Of The University Of Pennsylvania||Method of depositing calcium phosphate cermamics for bone tissue calcification enhancement|
|US5068122 *||Nov 8, 1989||Nov 26, 1991||Kyoto University||Process for forming a bioactive hydroxyapatite film|
|US5084300 *||May 2, 1990||Jan 28, 1992||Forschungszentrum Julich Gmbh||Apparatus for the ablation of material from a target and coating method and apparatus|
|US5085166 *||May 7, 1990||Feb 4, 1992||Mitsubishi Denki Kabushiki Kaisha||Laser vapor deposition apparatus|
|1||Barthell et al., "Ion Beam Deposition of Calcium Hydroxyapatite," Biomedi Materials and Devices, vol. 110, pp. 709-713 (1989).|
|2||*||Barthell et al., Ion Beam Deposition of Calcium Hydroxyapatite, Biomedical Materials and Devices, vol. 110, pp. 709 713 (1989).|
|3||Ducheyne et al., "Structural Analysis of Hydroxyapatite Coatings on Titanium," Biomaterials 7 (2), 1987 97-103.|
|4||*||Ducheyne et al., Structural Analysis of Hydroxyapatite Coatings on Titanium, Biomaterials 7 (2), 1987 97 103.|
|5||Ruckenstein et al., "A Nondesctructive Approach to Characterize Deposits on Various Surfaces", Journal of Colloid and Interface Science, vol. 96, No. 1, 1983, pp. 245-250.|
|6||*||Ruckenstein et al., A Nondesctructive Approach to Characterize Deposits on Various Surfaces , Journal of Colloid and Interface Science, vol. 96, No. 1, 1983, pp. 245 250.|
|7||*||Solnick Legg, Ion Beam and Plasma Technology for Improved Biocompatible Surfaces, MRS Bulletin, 1989, pp. 27 30.|
|8||Solnick-Legg, "Ion Beam and Plasma Technology for Improved Biocompatible Surfaces," MRS Bulletin, 1989, pp. 27-30.|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US5380298 *||Apr 7, 1993||Jan 10, 1995||The United States Of America As Represented By The Secretary Of The Navy||Medical device with infection preventing feature|
|US5406906 *||Jan 18, 1994||Apr 18, 1995||Ford Motor Company||Preparation of crystallographically aligned films of silicon carbide by laser deposition of carbon onto silicon|
|US5468930 *||Mar 10, 1993||Nov 21, 1995||Matsushita Electric Industrial Co., Ltd.||Laser sputtering apparatus|
|US5490912 *||May 31, 1994||Feb 13, 1996||The Regents Of The University Of California||Apparatus for laser assisted thin film deposition|
|US5607899 *||Feb 24, 1995||Mar 4, 1997||Sumitomo Electric Industries, Ltd.||Method of forming single-crystalline thin film|
|US5672284 *||Mar 1, 1996||Sep 30, 1997||Zimmer, Inc.||Method of making orthopaedic implant by welding|
|US5681575 *||May 7, 1993||Oct 28, 1997||Westaim Technologies Inc.||Anti-microbial coating for medical devices|
|US5711810 *||Dec 4, 1996||Jan 27, 1998||The United States Of America As Represented By The Secretary Of The Army||Apparatus for variable optical focusing for processing chambers|
|US5725914 *||Sep 26, 1995||Mar 10, 1998||Deutsche Forschungsanstalt fuer Luft - und Raumfahrt e.V.||Process and apparatus for producing a functional structure of a semiconductor component|
|US5730598 *||Mar 7, 1997||Mar 24, 1998||Sulzer Calcitek Inc.||Prosthetic implants coated with hydroxylapatite and process for treating prosthetic implants plasma-sprayed with hydroxylapatite|
|US5733609 *||Jun 1, 1993||Mar 31, 1998||Wang; Liang||Ceramic coatings synthesized by chemical reactions energized by laser plasmas|
|US5753251 *||Jun 2, 1995||May 19, 1998||Westaim Technologies, Inc.||Anti-microbial coating for medical device|
|US5770255 *||Sep 29, 1993||Jun 23, 1998||Westaim Technologies, Inc.||Anti-microbial coating for medical devices|
|US5773789 *||May 23, 1996||Jun 30, 1998||Bristol-Myers Squibb Company||Method of making an orthopaedic implant having a porous metal pad|
|US5837275 *||Jun 2, 1995||Nov 17, 1998||Westaim Technologies, Inc.||Anti-microbial materials|
|US5958440 *||Nov 18, 1993||Sep 28, 1999||Westaim Technologies, Inc.||Anti-microbial materials|
|US5973222 *||Jan 16, 1998||Oct 26, 1999||Bristol-Myers Squibb Co.||Orthopedic implant having a porous metal pad|
|US5985308 *||Feb 2, 1994||Nov 16, 1999||Westaim Technologies, Inc.||Process for producing anti-microbial effect with complex silver ions|
|US6017553 *||Jun 2, 1995||Jan 25, 2000||Westaim Technologies, Inc.||Anti-microbial materials|
|US6049054 *||Aug 21, 1997||Apr 11, 2000||Bristol-Myers Squibb Company||Method of making an orthopaedic implant having a porous metal pad|
|US6120857 *||May 18, 1998||Sep 19, 2000||The Regents Of The University Of California||Low work function surface layers produced by laser ablation using short-wavelength photons|
|US6238686||Jun 25, 1997||May 29, 2001||Westaim Technologies||Anti-microbial coating for medical devices|
|US6270861 *||Jun 7, 1995||Aug 7, 2001||Ut, Battelle Llc||Individually controlled environments for pulsed addition and crystallization|
|US6339913||Jul 10, 1998||Jan 22, 2002||Universidad De Vigo||Method for improving the osteointegration of osseus fixing implants|
|US6406745 *||Jun 6, 2000||Jun 18, 2002||Nanosphere, Inc.||Methods for coating particles and particles produced thereby|
|US6503578 *||May 5, 2000||Jan 7, 2003||National Science Council||Method for preparing ZnSe thin films by ion-assisted continuous wave CO2 laser deposition|
|US6660343||Oct 1, 2001||Dec 9, 2003||The United States Of America As Represented By The Secretary Of The Navy||Fabrication of conductive/non-conductive nanocomposites by laser evaporation|
|US6969474||Nov 5, 2003||Nov 29, 2005||Implant Innovations, Inc.||Implant surface preparation|
|US6984404||Nov 18, 1999||Jan 10, 2006||University Of Florida Research Foundation, Inc.||Methods for preparing coated drug particles and pharmaceutical formulations thereof|
|US7001672 *||Mar 26, 2004||Feb 21, 2006||Medicine Lodge, Inc.||Laser based metal deposition of implant structures|
|US7063748||Mar 13, 2002||Jun 20, 2006||Nanotherapeutics, Inc.||Methods for coating particles and particles produced thereby|
|US7118630 *||Aug 10, 2000||Oct 10, 2006||The Regents Of The University Of California||Apparatus for depositing a low work function material|
|US7169317||Jul 1, 2005||Jan 30, 2007||Implant Innovations, Inc.||Implant surface preparation|
|US7478637||Nov 9, 2004||Jan 20, 2009||Philip Morris Usa Inc.||Continuous process for surface modification of cigarette filter materials|
|US7547399||Jan 9, 2007||Jun 16, 2009||Biomet 3I, Llc||Implant surface preparation|
|US7550091||Feb 19, 2008||Jun 23, 2009||Biomet 3I, Llc||Implant surface preparation|
|US7632575 *||Oct 18, 2005||Dec 15, 2009||IMDS, Inc.||Laser based metal deposition (LBMD) of implant structures|
|US7666522 *||May 10, 2006||Feb 23, 2010||IMDS, Inc.||Laser based metal deposition (LBMD) of implant structures|
|US7857987||Feb 13, 2008||Dec 28, 2010||Biomet 3I, Llc||Implant surface preparation|
|US7985367 *||Jul 31, 2009||Jul 26, 2011||The Regents Of The University Of California||Method for producing active glass nanoparticles by laser ablation|
|US8067054||Apr 5, 2007||Nov 29, 2011||Boston Scientific Scimed, Inc.||Stents with ceramic drug reservoir layer and methods of making and using the same|
|US8071156||Mar 4, 2009||Dec 6, 2011||Boston Scientific Scimed, Inc.||Endoprostheses|
|US8187620||Mar 27, 2006||May 29, 2012||Boston Scientific Scimed, Inc.||Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents|
|US8216632||Nov 2, 2007||Jul 10, 2012||Boston Scientific Scimed, Inc.||Endoprosthesis coating|
|US8221499||Jan 25, 1999||Jul 17, 2012||Biomet 3I, Llc||Infection-blocking dental implant|
|US8221822 *||Jul 30, 2008||Jul 17, 2012||Boston Scientific Scimed, Inc.||Medical device coating by laser cladding|
|US8231980||Dec 3, 2009||Jul 31, 2012||Boston Scientific Scimed, Inc.||Medical implants including iridium oxide|
|US8251700||May 12, 2004||Aug 28, 2012||Biomet 3I, Llc||Surface treatment process for implants made of titanium alloy|
|US8287937||Apr 24, 2009||Oct 16, 2012||Boston Scientific Scimed, Inc.||Endoprosthese|
|US8353949||Sep 10, 2007||Jan 15, 2013||Boston Scientific Scimed, Inc.||Medical devices with drug-eluting coating|
|US8431149||Feb 27, 2008||Apr 30, 2013||Boston Scientific Scimed, Inc.||Coated medical devices for abluminal drug delivery|
|US8449603||Jun 17, 2009||May 28, 2013||Boston Scientific Scimed, Inc.||Endoprosthesis coating|
|US8454987 *||Mar 14, 2007||Jun 4, 2013||Kinki University||Biocompatible transparent sheet, method for producing the same, and cultured cell sheet used the same sheet|
|US8486073 *||Feb 23, 2007||Jul 16, 2013||Picodeon Ltd Oy||Coating on a medical substrate and a coated medical product|
|US8574615||May 25, 2010||Nov 5, 2013||Boston Scientific Scimed, Inc.||Medical devices having nanoporous coatings for controlled therapeutic agent delivery|
|US8617672 *||Jul 13, 2005||Dec 31, 2013||Applied Materials, Inc.||Localized surface annealing of components for substrate processing chambers|
|US8771343||Jun 15, 2007||Jul 8, 2014||Boston Scientific Scimed, Inc.||Medical devices with selective titanium oxide coatings|
|US8815273||Jul 27, 2007||Aug 26, 2014||Boston Scientific Scimed, Inc.||Drug eluting medical devices having porous layers|
|US8815275||Jun 28, 2006||Aug 26, 2014||Boston Scientific Scimed, Inc.||Coatings for medical devices comprising a therapeutic agent and a metallic material|
|US8900292||Oct 6, 2009||Dec 2, 2014||Boston Scientific Scimed, Inc.||Coating for medical device having increased surface area|
|US8920491||Apr 17, 2009||Dec 30, 2014||Boston Scientific Scimed, Inc.||Medical devices having a coating of inorganic material|
|US8932346||Apr 23, 2009||Jan 13, 2015||Boston Scientific Scimed, Inc.||Medical devices having inorganic particle layers|
|US9205030 *||Jan 29, 2013||Dec 8, 2015||Kinki University||Hard tissue regeneration material and hard tissue regeneration method|
|US9284409||Jul 17, 2008||Mar 15, 2016||Boston Scientific Scimed, Inc.||Endoprosthesis having a non-fouling surface|
|US9481608||Nov 22, 2013||Nov 1, 2016||Applied Materials, Inc.||Surface annealing of components for substrate processing chambers|
|US20010004711 *||Jan 25, 1999||Jun 21, 2001||Richard J. Lazzara||Infection-blocking dental implant|
|US20020106461 *||Mar 13, 2002||Aug 8, 2002||Nanosphere, Inc.||Methods for coating particles and particles produced thereby|
|US20040086661 *||Mar 12, 2002||May 6, 2004||Antti Yli-Urpo||Sintering of bioactive glass with localised electromagnetic and/or acoustic energy|
|US20040148031 *||Nov 5, 2003||Jul 29, 2004||Beaty Keith D.||Implant surface preparation|
|US20040265780 *||May 12, 2004||Dec 30, 2004||Robb T. Tait||Surface treatment process for implants made of titanium alloy|
|US20050123672 *||Mar 26, 2004||Jun 9, 2005||Justin Daniel F.||Laser based metal deposition of implant structures|
|US20060009857 *||Jul 8, 2004||Jan 12, 2006||Gibbs Phillip M||Method and apparatus for surface hardening implants|
|US20060051522 *||Jan 22, 2003||Mar 9, 2006||Talton James D||Method of pulsed laser assisted surface modification|
|US20060073356 *||Oct 18, 2005||Apr 6, 2006||Justin Daniel F||Laser based metal deposition (LBMD) of implant structures|
|US20060096605 *||Nov 9, 2004||May 11, 2006||Philip Morris Usa Inc.||Continuous process for surface modification of filter materials|
|US20060127443 *||Dec 9, 2004||Jun 15, 2006||Helmus Michael N||Medical devices having vapor deposited nanoporous coatings for controlled therapeutic agent delivery|
|US20070014949 *||Jul 13, 2005||Jan 18, 2007||Applied Materials, Inc.||Localized surface annealing of components for substrate processing chambers|
|US20070108162 *||Jan 9, 2007||May 17, 2007||Beaty Keith D||Implant surface preparation|
|US20070202351 *||May 10, 2006||Aug 30, 2007||Justin Daniel F||Laser based metal deposition (LBMD) of implant structures|
|US20080135521 *||Feb 13, 2008||Jun 12, 2008||Beaty Keith D||Implant surface preparation|
|US20080160168 *||Feb 19, 2008||Jul 3, 2008||Beaty Keith D||Implant surface preparation|
|US20080294236 *||May 23, 2007||Nov 27, 2008||Boston Scientific Scimed, Inc.||Endoprosthesis with Select Ceramic and Polymer Coatings|
|US20090012523 *||Feb 23, 2007||Jan 8, 2009||Picodeon Ltd Oy||Coating on a Medical Substrate and a Coated Medical Product|
|US20090118812 *||Nov 2, 2007||May 7, 2009||Boston Scientific Scimed, Inc.||Endoprosthesis coating|
|US20090149942 *||Jul 17, 2008||Jun 11, 2009||Boston Scientific Scimed, Inc.||Endoprosthesis having a non-fouling surface|
|US20090311297 *||Mar 14, 2007||Dec 17, 2009||Shigeki Hontsu||Biocompatible Transparent Sheet, Method for Producing the Same, and Cultured Cell Sheet Used the Same Sheet|
|US20100047434 *||Aug 21, 2008||Feb 25, 2010||Biomet Manufacturing Corp.||Fabrication of monolithic zones on porous scaffold|
|US20100072645 *||Jul 31, 2009||Mar 25, 2010||The Regents Of The University Of California||Method for producing active glass nanoparticles by laser ablation|
|US20110089041 *||Oct 19, 2009||Apr 21, 2011||Biomet Manufacturing Corp.||Methods of depositing discrete hydroxyapatite regions on medical implants|
|US20130236856 *||Jan 29, 2013||Sep 12, 2013||Kinki University||Hard tissue regeneration material and hard tissue regeneration method|
|USH1933 *||Apr 8, 1996||Jan 2, 2001||The United States Of America As Represented By The Secretary Of The Air Force||Magnetron sputter-pulsed laser deposition system and method|
|USRE37718||Apr 2, 1997||May 28, 2002||Southwest Research Institute||Ion beam modification of bioactive ceramics to accelerate biointegration of said ceramics|
|EP0678285A2 *||Apr 12, 1995||Oct 25, 1995||Bristol-Myers Squibb Company||Orthopaedic implant and method of making same|
|EP0678285A3 *||Apr 12, 1995||Jan 31, 1996||Squibb Bristol Myers Co||Orthopaedic implant and method of making same.|
|WO1994022513A1 *||Apr 7, 1994||Oct 13, 1994||The Government Of The United States Of America, As Represented By The Secretary Of The Navy||Medical device with infection preventing feature|
|WO1996004027A1 *||Jul 27, 1995||Feb 15, 1996||Southwest Research Institute||Ion beam modification of bioactive ceramics to accelerate biointegration of said ceramics|
|WO1996016196A2 *||Nov 20, 1995||May 30, 1996||The University Of Nottingham||Laser deposition of coatings|
|WO1996016196A3 *||Nov 20, 1995||Jul 18, 1996||Univ Nottingham||Laser deposition of coatings|
|WO1998021380A1 *||Nov 10, 1997||May 22, 1998||Universidad De Vigo||Method for improving the osteointegration of osseous fixing implants|
|WO1998053767A1 *||May 28, 1998||Dec 3, 1998||The Government Of The United States, As Represented By The Secretary Of The Navy||Method of producing a film coating by matrix assisted pulsed laser deposition|
|WO1999042631A1 *||Feb 18, 1999||Aug 26, 1999||Universidad De Vigo||Biocompatible coatings produced by means of laser|
|WO2000037122A1 *||Dec 21, 1999||Jun 29, 2000||Johannes Heitz||Fluoropolymer coating and method for the production thereof|
|WO2002074353A1 *||Mar 12, 2002||Sep 26, 2002||Vivoxid Oy||Sintering of bioactive glass with localised electromagnetic and/or acoustic energy|
|WO2003060181A1 *||Oct 11, 2002||Jul 24, 2003||Diro, Inc.||Bioactive device having surface with alloyed layer of calcium phosphate compounds and method of making|
|WO2005102684A1 *||Nov 30, 2004||Nov 3, 2005||Medicinelodge, Inc.||Laser based metal deposition of implant structures|
|WO2007096476A2 *||Feb 23, 2007||Aug 30, 2007||Picodeon Ltd Oy||Coating on a medical substrate and a coated medical product|
|WO2007096476A3 *||Feb 23, 2007||Nov 8, 2007||Picodeon Ltd Oy||Coating on a medical substrate and a coated medical product|
|WO2007096483A3 *||Feb 23, 2007||Oct 18, 2007||Picodeon Ltd Oy||Coating on a stone or ceramic substrate and a coated stone or ceramic product|
|U.S. Classification||427/2.27, 204/298.02, 427/255.28, 427/533, 427/596, 427/586, 427/255.21|
|International Classification||A61F2/30, C23C14/08, A61F2/00, A61L27/32, C23C14/28|
|Cooperative Classification||A61L27/32, C23C14/28, C23C14/08, A61F2310/00796, A61F2002/3097, A61F2/30767|
|European Classification||C23C14/08, A61F2/30L, C23C14/28, A61L27/32|
|Jan 27, 1992||AS||Assignment|
Owner name: UNITED STATES OF AMERICA, THE, AS REPRESENTED BY T
Free format text: ASSIGNS THE ENTIRE INTEREST. SUBJECT TO LICENSE RECITED;ASSIGNORS:COTELL, CATHERINE M.;CHRISEY, DOUGLAS B.;GRABOWSKI, KENNETH S.;AND OTHERS;REEL/FRAME:005996/0121;SIGNING DATES FROM 19910729 TO 19910730
Owner name: UNITED STATES OF AMERICA, THE, AS REPRESENTED BY T
Free format text: ASSIGNS THE ENTIRE INTEREST. SUBJECT TO LICENSE RECITED;ASSIGNORS:COTELL, CATHERINE M.;CHRISEY, DOUGLAS B.;GRABOWSKI, KENNETH S.;AND OTHERS;SIGNING DATES FROM 19910729 TO 19910730;REEL/FRAME:005996/0121
|Feb 3, 1997||FPAY||Fee payment|
Year of fee payment: 4
|Apr 3, 2001||REMI||Maintenance fee reminder mailed|
|Sep 9, 2001||LAPS||Lapse for failure to pay maintenance fees|
|Nov 13, 2001||FP||Expired due to failure to pay maintenance fee|
Effective date: 20010907